Source:http://linkedlifedata.com/resource/pubmed/id/16538176
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2006-3-15
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| pubmed:abstractText |
The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
1744-6872
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| pubmed:author |
pubmed-author:ChangYun-TingYT,
pubmed-author:ChenGwo-ShingGS,
pubmed-author:ChenWei-HsuanWH,
pubmed-author:ChenWen-ChiehWC,
pubmed-author:ChenYuan-TsongYT,
pubmed-author:ChungWen-HungWH,
pubmed-author:FangWu-HsiangWH,
pubmed-author:HsiaoPa-FanPF,
pubmed-author:HuShu-LingSL,
pubmed-author:HuangYau-LiYL,
pubmed-author:HungShuen-IuSI,
pubmed-author:JeeShiou-HwaSH,
pubmed-author:LeeWoan-RuohWR,
pubmed-author:LinJuei-JuengJJ,
pubmed-author:LouYi-HuiYH,
pubmed-author:ShihHan-YuHY,
pubmed-author:WeiChun-YuCY,
pubmed-author:WongTak-WahTW,
pubmed-author:WuMeng-TseMT
|
| pubmed:issnType |
Print
|
| pubmed:volume |
16
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
297-306
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:16538176-Anticonvulsants,
pubmed-meshheading:16538176-Carbamazepine,
pubmed-meshheading:16538176-Case-Control Studies,
pubmed-meshheading:16538176-Drug Hypersensitivity,
pubmed-meshheading:16538176-Epidermal Necrolysis, Toxic,
pubmed-meshheading:16538176-Exanthema,
pubmed-meshheading:16538176-Genetic Predisposition to Disease,
pubmed-meshheading:16538176-HLA-B Antigens,
pubmed-meshheading:16538176-Haplotypes,
pubmed-meshheading:16538176-Humans,
pubmed-meshheading:16538176-Stevens-Johnson Syndrome
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| pubmed:year |
2006
|
| pubmed:articleTitle |
Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions.
|
| pubmed:affiliation |
Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road Section 2, Nankang, Taipei, Taiwan.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|